AB1328 LONGITUDINAL SEROLOGICAL STUDY OF ANTI-SARS-CoV-2 SPIKE PROTEIN ANTIBODIES AFTER TWO DOSES OF mRNA VACCINES IN PATIENTS WITH RHEUMATIC DISEASES: ANALYSIS OF EFFECTS OF IMMUNOSUPPRESSANT THERAPY
Authors: M. Kawazoe, K. Aoki, W. Hirose, S. Masuoka, K. Kaneko, J. Nishio, E. Watanabe, K. Furukawa, M. Kanaji, T. Nanki
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The longitudinal efficacy and safety data of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with rheumatic disease (RD) remains unclear. <h3>Objectives</h3> The objective of the study was to examine changes over time in anti-SARS-CoV-2 spike protein IgG (anti-S IgG) values in RD patients compared with controls and investigate the effects of immunosuppressants on the values. Safety of vaccine was also evaluated. <h3>Methods</h3> RD patients receiving glucocorticoids or immunosuppressants who were scheduled to receive two doses of SARS-CoV-2 mRNA vaccines were included. Patients not receiving these drugs and were attending the hospital for diseases other than RD or malignancies served as the control group (CG). Following the guidance of the American College of Rheumatology, some immunosuppressive drugs were withheld before and after vaccinations. Blood samples were collected before and 1, 3, and 6 months (M1, M3, M6) after the vaccinations, and anti-S IgG values were measured using SARS-CoV-2 IgG II Quant Reagent Kit (Abbott Laboratories, USA). <h3>Results</h3> BNT162b2 mRNA vaccine-received 289 RD patients {mean age 66.9 [standard deviation (SD), 12.6] years; 241 females and 48 males} and 33 controls (mean age 70.7 [SD, 7.8] years; 22 females and 11 males) were mainly analyzed. Anti-S IgG values markedly increased in both groups at M1 [CG; 9751.5 (2385.3 – 21506.1), RD; 2300.8 (188.5 – 7671.7) AU/mL, expressed as median (25th to 75th percentiles)], subsequently decreased, and were significantly lower in the RD group than in the CG at all time points [CG; 5012.2 (2933.3 – 6628.4), RD; 1505.0 (459.0 – 3229.0) at M3, CG; 1353.6 (505.8 – 1910.3), RD; 402.0 (130.5 – 836.2) at M6]. Regarding antibody positivity, all patients in the CG tested positive at all time points. The antibody positivity rate was significantly lower in the RD group (85.0% at M1, 92% at M3, 86.4% at M6). In comparisons by disease, anti-S IgG values were significantly lower in patients with rheumatoid arthritis, systemic lupus erythematosus, vasculitis and dermatomyositis/polymyositis. In comparisons by treatment, anti-S IgG values were significantly lower in patients receiving rituximab [8.9 (5.8 – 68.2) at M1, 51.7 (26.4 – 144.0) at M3, 45.3 (23.1 – 67.4) at M6], mycophenolate mofetil [258.4 (1.1 – 713.7), 395.1 (18.0 – 2096.1), 212.3 (14.2 – 458.9)], cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig) [336.8 (33.5 – 1166.7), 324.9 (111.2 – 480.6), 84.0 (37.9 – 118.7)], and prednisolone (PSL) [449.4 (26.3 – 2920.1), 709.6 (135.3 – 2008.5), 201.4 (44.7 – 602.5)]. A multivariate analysis with a linear mixed model indicated that there was a significant inverse association between age and the extent of changes in anti-S IgG values from M1, indicating greater decreases in antibody values at an older age from M1 [-75 (-133 – -18), expressed as regression coefficient (95% confidence interval)]. The extent of the decrease in anti-S IgG values was also significantly greater in males [-1873 (-3604 – -142)] and patients treated with PSL [-2071 (-3590 – -551)], CTLA4-Ig [-4018 (-6606 – -1429)], TNF inhibitors [-2009 (-3861 – -157)], and IL-6 inhibitors [-2422 (-4488 – -355)]. Adverse reactions were similar in both the CG and RD group. <h3>Conclusion</h3> These results showed that SARS-CoV-2 mRNA vaccination is effective and safe in patients with RD treated with a variety of immunosuppressants. However, even following the ACR guidance on withholding dugs, anti-S IgG values were lower and significantly decreased over time depending on disease and immunosuppressive drugs. Therefore, relative short-term repetitive vaccination might be warranted in patients with RD receiving immunosuppressive drugs. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Mai Kawazoe Speakers bureau: Ayumi Pharmaceutical Corporation, Asahi Kasei Pharma Corp, AstraZeneca K.K., Gilead Sciences Inc and GlaxoSmithKline K.K., Kotaro Aoki: None declared, Wataru Hirose Speakers bureau: Pfizer Japan Inc., Asahikasei Pharma Corp., Chugai Pharmaceutical Co., AbbVie GK and Mitsubishi-Tanabe Pharma Co., Shotaro Masuoka: None declared, Kaichi Kaneko Speakers bureau: Asahi Kasei Pharma Corp, AstraZeneca K.K.,Boehringer Ingelheim Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K.,Gilead Sciences Inc, GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Novartis Pharma K.K. and Pfizer Japan Inc., Grant/research support from: Asahi Kasei Pharma Corp, Boehringer Ingelheim Co., Ltd. and Daiichi Sankyo Co., Ltd., Junko Nishio Speakers bureau: Asahi KASEI Pharma and Taisho Pharmaceutical Holdings., Grant/research support from: Asahi KASEI Pharma, CHUGAI PHARMACEUTIAL CO., LTD., ONO PHARMACEUTIAL CO., LTD., Boehringer Ingelheim, Nippon KAYAKU CO., AYUMI Pharmaceutical CO., Abbvie GK, Abbott Japan LLC and Taisho Pharmaceutical Holdings., Eri Watanabe Grant/research support from: GlaxoSmithKline K.K., Karin Furukawa: None declared, Miwa Kanaji: None declared, Toshihiro Nanki Speakers bureau: Eisai Co., Ltd., Astellas Pharma Inc., Janssen Pharmaceutical K.K., Ayumi Pharmaceutical Corporation, Pfizer Japan Inc., Asahikasei Pharma Corp., Eli Lilly Japan K.K., Takeda Pharmaceutical Co., Nippon Boehringer Ingelheim Co., Ltd., isho Pharmaceutical Co., Ltd., UCB Japan Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., GlaxoSmithKline plc., and AbbVie GK., Consultant of: UCB Japan Co., Ltd., Eisai Co., Ltd., and Chugai Pharmaceutical Co., Grant/research support from: Chugai Pharmaceutical Co., Eisai Co., Ltd., Teijin Pharma Ltd., Eli Lilly Japan K.K., Bristol-Myers K.K., Ono Pharmaceutical Co., Ltd., Asahikasei Pharma Corp., Mitsubishi-Tanabe Pharma Co., Ayumi Pharmaceutical Corporation, Shionogi &amp; Co., Ltd., Nippon Kayaku Co., Ltd., AbbVie GK, Nippon Boehringer Ingelheim Co., Ltd., Abbott Japan LLC and Taisho Pharmaceutical Co., Ltd.